New insight into the human genome through the lens of evolution

Jul 11, 2013

By comparing the human genome to the genomes of 34 other mammals, Australian scientists have described an unexpectedly high proportion of functional elements conserved through evolution.

Less than 1.5% of the is devoted to conventional genes, that is, encodes for proteins. The rest has been considered to be largely junk. However, while other studies have shown that around 5-8% of the is conserved at the level of DNA sequence, indicating that it is functional, the new study shows that in addition much more, possibly up to 30%, is also conserved at the level of RNA structure.

DNA is a biological blueprint that must be copied into another form before it can be actualised. Through a process known as 'transcription', DNA is copied into RNA, some of which 'encodes' the proteins that carry out the biological tasks within our cells. Most RNA molecules do not code for protein, but instead perform regulatory functions, such as determining the ways in which genes are expressed.

Like infinitesimally small Lego blocks, the nucleic acids that make up RNA connect to each other in very specific ways, which force RNA molecules to twist and loop into a variety of complicated 3D structures.

Dr Martin Smith and Professor John Mattick, from Sydney's Garvan Institute of Medical Research, devised a method for predicting these complex RNA structures – more accurate than those used in the past – and applied it to the genomes of 35 different mammals, including bats, mice, pigs, cows, dolphins and humans. At the same time, they matched mutations found in the genomes with consistent RNA structures, inferring conserved function. Their findings are published in Nucleic Acids Research, now online.

"Genomes accumulate mutations over time, some of which don't change the structure of associated RNAs. If the sequence changes during evolution, yet the RNA structure stays the same, then the principles of natural selection suggest that the structure is functional and is required for the organism," explained Dr Martin Smith.

"Our hypothesis is that structures conserved in RNA are like a common template for regulating gene expression in mammals – and that this could even be extrapolated to vertebrates and less complex organisms."

"We believe that RNA structures probably operate in a similar way to proteins, which are composed of structural domains that assemble together to give the protein a function."

"We suspect that many RNA structures recruit specific molecules, such as proteins or other RNAs, helping these recruited elements to bond with each other. That's the general hypothesis at the moment – that non-coding RNAs serve as scaffolds, tethering various complexes together, especially those that control genome organization and expression during development."

"We know that many RNA transcripts are associated with diseases and developmental conditions, and that they are differentially expressed in distinct cells."

"Our structural predictions can serve as an annotative tool to help researchers understand the function of these RNA transcripts."

"That is the first step – the next is to describe the structures in more detail, figure out exactly what they do in the cell, then work out how they relate to our normal development and to disease."

Explore further: Fungi enhances crop roots and could be a future 'bio-fertilizer'

Related Stories

Decoding mystery sequences involved in gene regulation

Jul 10, 2013

Every cell in an organism's body has the same copy of DNA, yet different cells do different things; for example, some function as brain cells, while others form muscle tissue. How can the same DNA make different things happen? ...

The genome's 3D structure shapes how genes are expressed

Jun 23, 2013

Scientists from Australia and the United States bring new insights to our understanding of the three-dimensional structure of the genome, one of the biggest challenges currently facing the fields of genomics ...

Recommended for you

Scientists identify protein profiles of DNA repair

13 hours ago

During each cell division, more than 3.3 billion base pairs of genomic DNA have to be duplicated and segregated accurately to daughter cells. But what happens when the DNA template is damaged in such a way ...

Low-allergen soybean could have high impact

19 hours ago

In the United States, nearly 15 million people and 1 in 13 children suffer from food allergy. In Arizona alone, every classroom contains at least two children with a food allergy.

Study shows where damaged DNA goes for repair

May 03, 2015

A Tufts University study sheds new light on the process by which DNA repair occurs within the cell. In research published in the May 15 edition of the journal Genes & Development and available May 4 onli ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.